Microwave Assisted One-pot Synthesis Bull. Korean Chem. Soc. 2010, Vol. 31, No. 7 1863 DOI 10.5012/bkcs.2010.31.7.1863 Microwave Assisted One-pot Synthesis of Novel α -Aminophosphonates and Their Biological Activity Alahari Janardhan Rao, Pasupuleti Visweswara Rao, † Valsani Koteswara Rao, Challamchalla Mohan, Chamarthi Naga Raju, * and Cirandur Suresh Reddy Department of Chemistry, Sri Venkateswara University, Tirupati - 517 502, India. * E-mail: rajuchamarthi10@gmail.com † Department of Biotechnology, Sri Venkateswara University, Tirupati - 517 502, India Received February 3, 2010, Accepted March 12, 2010 A simple and efficient synthesis of various α-aminophosphonates (3a-l) by the reaction of substituted aromatic/hetero- cyclic aldehydes, 2-amino-6-methoxy-benzothiazole and dibutyl/diphenyl phosphites under microwave irradiation without catalyst was accomplished. The phosphonates were characterized by elemental analysis, IR, 1 H, 13 C- and 31 P- NMR spectra. They showed promising antimicrobial, anti-oxidant activities depending on the nature of bioactive groups at the α-carbon. Key Words: Aminophosphonates, Microwave irradiation, Gram positive bacteria, Gram negative bacteria, Anti-oxidant activity Introduction Kabachnik-Fields reaction is one of the most effective syn- thetic methods for α-aminophosphonates. A great deal of atten- tion is bestowed on them 1,2 as they are structural analogues of the corresponding α-amino acids. Further, heterocyclic phosphonat- es and ω-aminophosphonates are an important class of com- pounds, with several potential applications in medicine as anti- cancer agents, 3 potent enzyme inhibitors, 4 antiviral agents, 5 pep- tide mimetics, 6 haptens of catalytic antibodies, antibiotics, and pharmacological agents. 7 Their diverse applications include in- hibition of synthase, 8 HIV protease, 9 renin, 10 and PTPases. 11,12 Some of these derivatives are potential antibiotics. 13 The ami- nophosphonic and aminophosphinic acids are of considerable interest due to their applications as agrochemicals such as plant growth regulators, pesticides and herbicides. 14 Besides the com- pounds containing benzothiazole moiety have been reported to have excellent fungicidal activity. 15-17 A variety of synthetic ap- proaches have been reported for them. Of all the methods, the nucleophilic addition of phosphites to imines, catalyzed by Lew- is acid or a base is the most convenient one. Nowadays, microwave irradiation is used to accomplish cer- tain unsuccessful or low-yielding reactions, reducing the re- action time from days to minutes, and improving yields. 18,19 Synthesis of α-aminophosphonates under microwave conditions has been scarcely investigated. We report the synthesis of α-aminophosphonates using 2- amino-6-methoxy benzothiazole, various substituted aromatic/ heterocyclic aldehydes and dibutyl/diphenyl phosphite in dry toluene under microwave irradiation in excellent yields, in a very short reaction times. Experimental Chemistry. Sigma-Aldrich, Merck and Lancaster Chemicals were used as such. Solvents used for spectroscopic and other physical studies were reagent grade and were further purified by literature methods. 28 The reactions were carried out on Micro- wave Oven, CATALYST-4R, Research Model, Made in India. Melting points were determined by Guna Digital Melting Point apparatus using a calibrated centigrade thermometer. IR spectra were obtained in KBr on a Perkin-Elmer Model 281-B spec- trophotometer, in wave numbers (cm ‒1 ). 1 H and 13 C NMR spec- tra were recorded in DMSO-d6 on a Bruker AVANCE III 500 MHz spectrometer operating at 500 MHz for 1 H, 125 MHz for 13 C and 202.4 MHz for 31 P NMR. The 1 H and 13 C chemical shifts were expressed in ppm with reference to tetramethylsilane and 31 P chemical shifts to 85% H 3 PO 4 . Mass spectra were recorded on a JEOL GCMATE II GC Mass spectrometer. Elemental an- alyses were performed by Central Drug Research Institute, Lucknow, India. General procedure for the preparation of 3a-l. Conventional method: To a solution of 2-amino-6-methoxy benzothiazole (1) (0.005 mol) and various aromatic/heterocyclic aldehydes (2) (0.005 mol) in anhydrous toluene (15 mL), dibut- yl/diphenyl phosphite (0.005 mol) in anhydrous toluene (10 mL) was added dropwise with stirring at room temperature for half an hour. The reaction mixture was refluxed with stirring for 4 - 5 h. After completion of the reaction as indicted by TLC, ethyl- acetate:methanol, 4:1, the solvent was removed in a rota-evapo- rator, the residue was purified by column chromatography on silica gel (60 - 120 mesh) using petroleum ether-ethyl acetate (2:8) as eluent. Physical, analytical and IR spectral data of 3a-l are given in the respective compounds. Yields of 3a-l are in the range of 62 - 73% Microwave irradiation: 2-Amino 6-methoxy benzothiazole (1) (0.005 mol) was treated with 1 equiv. of substituted various aromatic/ heterocyclic aldehydes (2) (0.005 mol) and 1 equiv. of dibutyl/diphenyl phosphite (0.005 mol), in anhydrous toluene were irradiated in a microwave (700 Watts), for 12 - 15 min. These are the optimized conditions for the best results. Yields of 3a-l are in the range of 81 - 88%. Dibutyl(6-methoxybenzo[d]thiazol-2-ylamino)(thiophen- 2-yl)methylphosphonate(3a): Yield 83%. mp 177 - 182 o C. IR